Principles of antidote pharmacology: an update on prophylaxis, post‐exposure treatment recommendations and research initiatives for biological agents

Abstract

The use of biological agents has generally been confined to military‐led conflicts. However, there has been an increase in non‐state‐based terrorism, including the use of asymmetric warfare, such as biological agents in the past few decades. Thus, it is becoming increasingly important to consider strategies for preventing and preparing for attacks by insurgents, such as the development of pre‐ and post‐exposure medical countermeasures. There are a wide range of prophylactics and treatments being investigated to combat the effects of biological agents. These include antibiotics (for both conventional and unconventional use), antibodies, anti‐virals, immunomodulators, nucleic acids (analogues, antisense, ribozymes and DNAzymes), bacteriophage therapy and micro‐encapsulation. While vaccines are commercially available for the prevention of anthrax, cholera, plague, Q fever and smallpox, there are no licensed vaccines available for use in the case of botulinum toxins, viral encephalitis, melioidosis or ricin. Antibiotics are still recommended as the mainstay treatment following exposure to anthrax, plague, Q fever and melioidosis. Anti‐toxin therapy and anti‐virals may be used in the case of botulinum toxins or smallpox respectively. However, supportive care is the only, or mainstay, post‐exposure treatment for cholera, viral encephalitis and ricin – a recommendation that has not changed in decades. Indeed, with the difficulty that antibiotic resistance poses, the development and further evaluation of techniques and atypical pharmaceuticals are fundamental to the development of prophylaxis and post‐exposure treatment options. The aim of this review is to present an update on prophylaxis and post‐exposure treatment recommendations and research initiatives for biological agents in the open literature from 2007 to 2009.

Detection of Botulinum Neurotoxin Serotypes A and B Using a Chemiluminescent versus Electrochemiluminescent Immunoassay in Food and Serum

“…1 The only treatments available for botulism remain the use of respiratory aids (ventilators) and the neutralization of excess toxin in the bloodstream with an equine derived polyvalent anti-toxin serum or in the case of infant botulism, with the human derived antitoxin BabyBig. 4 The speed of recovery depends on quick diagnosis and treatment.…”

Biological Toxins and Bioterrorism

“…The active site of BoNT/A LC is characterized by HEXXH zinc-binding motif that coordinates the catalytic zinc ion through two His residues, a Glu 224 residue ligating the zinc via a water molecule and Glu 262 that acts as the fourth ligand (Vallee and Auld 1990;Kukreja et al 2007). Although the probability of an incident involving a biological agent is relatively low, the ability of minute amounts of these agents to cause great morbidity and mortality necessitates these biological agents to be classified as weapons of mass destruction (Ramasamy et al 2010). Structural elucidation of the LC in the presence of substrate has been instrumental in providing evidence for the presence of an array of substrate recognition and binding sites known as exosites that are remote from the active site (Fig.…”

“…Mice immunized with BoNT/A RYM survived subsequent challenges of 10,000 times that of BoNT/A LD 50 , thus making this approach viable in the production of future vaccines Ramasamy et al 2010). The potential use of a non-catalytic recombinant form of botulinum toxin was investigated wherein two single point mutations on the light chain domain rendered the toxin inactive and unable to cleave its substrate, SNAP-25.…”

“…The plasmid DNA replicon vaccine (pSCARSHc) encoding the BoNT/A HC provided better protection against BoNT/A in mice compared to a conventional plasmid DNA vaccine (pcDNASHc) encoding the same antigen (Ramasamy et al 2010). Plasmid DNA replicon vectors derived from alphaviruses were used to boost immune responses ).…”

<i>Bacillus anthracis</i> infections – new possibilities of treatment

“…This indicates that Raxibacumab can be used for prophylaxis and treatment of inhalational anthrax. In 2009, the HGS provided 20,000 doses of Raxibacumab to the Strategic National Stockpile [23,24,25,26].…”